Kinetics of the metabolism of four PET radioligands in living minipigs

Most radioligands are substantially metabolised in peripheral organs during the course of positron emission tomography (PET) recordings. Accurate dete rmination of plasma concentrations of unmetabolised radioligands is often i mportant for quantification of data from PET studies. The fractions of untr ansformed radioligand and radioactive metabolites in plasma extracts must t hen be measured. Temporal changes in these fractions are influenced by the rate constant of appearance of total radioactive metabolites in plasma (app arent rate constant of metabolism in plasma, k(0)) and the net rate constan t of elimination of all radioactive metabolites from plasma (k(-I)). In ord er to clarify the relationship between radioligand fractions and rate const ants, plasma samples collected from Gottingen minipigs during PET recording s using four different binding site ligands were analysed by radio high per formance liquid chromatography. The calculated plasma concentrations of par ent compounds and their radioactive metabolites were used to calculate k(0) and k(-1) for C-11-labelled NNC 112, NS 2214, PK 11195 and raclopride in m inipigs using a novel application of the tissue-slope intercept plot. In ge neral, the apparent rate constant of metabolism in plasma was found to be g reater in the minipig than in man. The reported kinetic analysis enables th e apparent metabolism of PET radioligands in plasma to be quantified. (C) 2 001 Elsevier Science Inc. All rights reserved.